Study shoots down AD drug class in mild patients

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The rush to develop Alzheimer's treatments that halt or idle the condition may have gotten some added fuel from a study showing medications known as cognitive enhancers failed to improve cognition or function among patients with mild forms of the disease.

In the study published in Canadian Medical Association's namesake journal Monday, researchers compared clinical trials held between 1999 and 2007 that tested the impact of four medications in this category. They found that while these drugs did nothing to stop decline, they did manage to offer up an increased risk for gastrointestinal side effects.

The focus was on patients who have memory loss and impaired cognitive function, but “no change in their basic daily functioning.” The “mild” label is a transitive one. Researchers noted that 3% to 7% of patients who qualify as having a mild forms of the Alzheimer's move toward dementia, and that this rate accelerates to between 11% and 33% within two years.

Using cognitive enhancers has been based on the hypothesis that the medications may slow the move from mild Alzheimer's to dementia, and the researchers looked at studies in which patients were given the Pfizer/Eisai medication Aricept (donepezil), Novartis's Exelon (rivastigmine), Janssen's Razadyne (galantamine) or Forest's Namenda (memantine). While these medications are not widely available for mild patients, researchers note that patients and families are increasingly asking to use the treatments when available.

The results: no difference in cognition after 36 weeks of follow-up among Aricept patients, or even in periods ranging from 24 to 156 weeks. Nor did researchers find any significant difference when comparing cognitive impact among patients taking other treatments. The medications also failed to provide a significant difference in mortality. The memory-destroying condition is the sixth leading cause of death, and the fifth leading cause of death among people 65 and over, according to the Alzheimer's Association. “There are no survivors,” the non-profit notes on its website.

Researchers noted that there is a very slim assessment window that makes it appear as though these medications do help mild patients when using the Alzheimer's Disease Assessment, which is among the array of diagnostic tools used among the studies. In this instance, investigators said they did find a statistically significant impact in favor of cognitive enhancers, but only when limited to a time frame of 12 to 84 weeks of follow-up, after which “this difference was absent beyond this point.”

The disease's cause remains elusive, and the industry is pursuing a variety of strategies that seek to address possible causes as well as symptoms. Elan, for example, has a Phase III treatment it licensed from Transition Therapeutics, which seeks to address aggression and agitation that appears in around 60% of patients, while Genentech is in the early stages of a five-year study of crenezumab among a population with a clear genetic link to the condition.

Repurposing drugs to treat Alzheimer's is also a tactic being pursued by both the industry and the National Institutes of Health. For Eli Lilly, this has meant testing solanezumab in a less severely affected population, while other are exploring the possibility that insulin could have a new role.

Among the research in favor of the diabetes-medication-as-Alzheimer's treatment is pilot study of 100 volunteers noted by the National Institutes of Aging, a subdivision of the NIH, that associated inhaled insulin with improving memory and slowing decline. Takeda and Zinfandel are already pursuing a variation of this, and is experimenting with the now off-patent diabetes medication Actos. An early stage animal study reported on Monday by PM Live showed that Novo's Victoza may also be a contender in the AD space.

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